POS0423 PLASMA METABOLOMIC PROFILES OF PATIENTS WITH ACTIVE PERIPHERAL PSORIATIC ARTHRITIS CAN DIFFERENTIATE TREATMENT RESPONDERS FROM FAILURES: EXPLORATORY FINDINGS FROM THE FLORA TRIAL
Authors: M. Skov Kragsnaes, J. Miguens Blanco, B. Mullish, J. I. Contreras-Serrano, H. C. Horn, H. Munk, J. K. Pedersen, A. C. Nilsson, K. Kristiansen, J. Kjeldsen, J. Marchesi, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Metabolite profiling of biofluids has an emergent role in exploring the contribution of host-microbiome interactions to the treatment response of immune-mediated arthritis.[1] <h3>Objectives</h3> As part of the FLORA trial (exploring the impact of gut microbiome manipulation upon response to methotrexate [MTX]),[2] we investigated plasma metabolomic profiles of adults with psoriatic arthritis (PsA) and whether they correlated with the primary trial outcome, which was clinical response to MTX (responder vs failure) following one faecal microbiota transplant (FMT) or sham transplant. <h3>Methods</h3> Thirty-one PsA patients with active peripheral disease, despite at least 3 months of steady-state dose MTX, were included in the 26-week, double-blind, parallel-group, 1:1 randomised, sham-controlled, superiority trial (FLORA trial; NCT03058900).[2] Patients were randomly allocated to receive either one gastroscopic-guided FMT (n = 15) or sham transplant (n = 16). Each FMT product encompassed 50 g of processed faeces obtained from one of four healthy, thoroughly screened donors. Patients continued MTX throughout the trial. The primary trial endpoint was the proportion of treatment failures through 26 weeks, defined as need for treatment escalation (in most cases instigation of TNF inhibitors) due to insufficient improvement of disease activity or disease worsening.[2] Li-Hep plasma samples were collected at baseline, week 4, 12, and 26. The metabolic profiles were measured using <sup>1</sup>H Nuclear Magnetic Resonance (NMR). We used a supervised multivariate orthogonal partial least squares-discriminant analysis (OPLS-DA) to model metabolic differences among groups. <h3>Results</h3> Twenty women and eleven men with a mean age of 50.7 years (SD = 13.6) and a mean swollen joint count of 7.1 (SD = 2.8) were included in the trial.[2] We were able to annotate 40 plasma metabolites in the baseline samples. No differences in baseline plasma profiles were observed between patients allocated to FMT and sham (OPLS-DA model; Q2 = -0.452, <i>p</i> = 1). However, the OPLS-DA analysis revealed a significant model for treatment responders (n = 19) vs failures (n = 12) among all patients, Figure 1. Correlations between metabolites and the primary trial outcome with a correlation coefficient (r) ≥0.50 are presented in Table 1. When patients were stratified for intervention type, the models continued to show significant separation (FMT arm: Q2 = 0.383, <i>p</i> &lt; 0.0001; sham arm: Q2 = 0.260, <i>p</i> = 0.002). In both the FMT and the sham models, glucose (r = 0.67 and r = 0.63) correlated positively with treatment failure while lysine (r = -0.83 and r = -0.65) and phenylacetate (r = -0.66 and r = -0.51) correlated with successful treatment response. <h3>Conclusion</h3> In the FLORA trial, plasma metabolomic profiles of patients with active, peripheral PsA significantly discriminated between treatment responders and failures. This discriminatory power was the case for the entire trial population as well as for each of the two treatment arms (FMT vs sham). <h3>References</h3> [1]Rizzo C, et al. Metabolomics: An Emerging Approach to Understand Pathogenesis and to Assess Diagnosis and Response to Treatment in Spondyloarthritis. Cells 2022;11(3):549. [2]Kragsnaes MS, et al. Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial. Ann Rheum Dis 2021; 80: 1158-1167. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.